Hemodynamics & Cellular Phases Types of Exudates (Role of Chemical mediators in inflammation)

Hemodynamics Hemodynamics consist of maintenance of: I-Vessel wall integrity. II-Intravascular pressure & osmalarity. III-Blood as liquid.

Hemodynamic Changes These are; I-Disturbances in cellular phases. II-Disturbances in blood. III-Non clot formation.

Hemodynamic Changes Disturbances in Cellular Phases: Disturbances occur in blood & endothelium, like: I-Changes in volume, pressure & proteins contents. II-Alteration in epithelial function. Both cause movements of water towards the vessel wall & out side the vessel in the interstitial tissue/spaces, called edema.

Edema (Changes in Volume & Pressure)

Hemodynamic Changes II-Disturbances in blood: Disturbance in fluidity of blood. Blood not maintain as fluid with injury, causes clot formation. Fixed clot formation in vessel wall lumen called Thrombosis.

Thrombosis

Thrombosis

Thrombosis

Thrombosis

Hemodynamic Changes II-Disturbances in blood: Migration of clot (thrombus) in the vessel lumen is called, Embolism. Obstruction in vessel lumen, by clot (thrombosis), obstruct the blood flow to the tissue, cause cell death (infarction).

Embolism

Infarction

Hemodynamic Changes III-Non clot formation: Inability to clot after vascular injury results in hemorrhage. Local bleeding cause, tissue perfusion. Extensive hemorrhage results in hypotension (shock) & death.

Types of Edema These are: I-Fluid collection in interstitial tissue cause edema. II-Inflammatory edema due to increase vascular permeability.

Types of Edema I-Fluid collection in interstitial tissue cause edema: There is sever or generalized edema with subcutaneous tissue swelling called Anasarca.

Types of Edema II-Inflammatory edema due to increase vascular permeability: i-Dependent edema. ii-Fluid collection (edema fluid) in the body cavities.

Types of Edema II-Inflammatory edema due to increse vascular permeability: i-Dependent edema; In feet. In legs. At sacral region.

Types of Edema II-Inflammatory edema due to increse vascular permeability: ii-Fluid collection (edema fluid) in the body cavities: Hydrothorax, (fluid in thoracic cavity). Hydropericardium, (fluid in pericardial cavity). Hydroperitoneum, (fluid in peritoneal cavity), also called Ascitis.

Hydrothorax

Hydropericardium

Ascitis.

Hyperermia & Congestion Hyperemia is an active process, occurs due to arteriole dilation, cause engorgement of vessels with oxygeneted blood. This occur as red area on body in; Inflammation. Skeletal muscle during exercise.

Hyperermia & Congestion Congestion is a passive process resulting from impaired blood out flow from a tissue Blue red color (cyanosis), can occur due to accumulation of deoxygeneted blood. Congestion can occur: Locally due to an isolated venous obstruction. Systematically in cardiac failure.

Hyperemia

Sub mucosal Congestion

Congestion

Exudate Formation In Inflammation  Vascular changes  Cardinal signs RUBOR (Redness ) – Increased arterial blood flow CALOR (Rise in temperature) – Increased arterial blood flow DOLOR ( Pain ) – Physical / Chemical irritation of nerve TUMOR (Swelling ) – Collection of exudate

Exudate Exudates it is an inflammatory extra vascular fluid that has a high protein concentration, cellular debris and an specific gravity above 1.020. There is also disturbance in the normal permeability of small blood vessels in the area of injury.

Types of exudate The types are: Serous. Fibrinous. Suppurative. Hemorrhegic. Ulceration.

Types of exudate Serous / Catarrhal Resorption (No complication) Watery, protein-poor effusion (e.g., blister) Fibrinous Fibrinolysed / Fibrosis (May or may not have complication) Fibrin accumulation. Either entirely removed or becomes fibrotic

Serous fluid in Pericardial Cavity

Types of exudate Suppurative Presence of pus (pyogenic staphylococcal species). Often walled-off if persistent. Haemorrhagic Adherence (Complication)

Hemorrhage

Types of exudate Ulceration Necrotic and eroded epithelial surface Underlying acute and chronic inflammation Trauma, toxins, vascular insufficiency

Chronic Inflammtion (Gastric Ulcer)

Chronic Inflammtion (Gastric Ulcer)

Chemical mediators Chemical mediators are the chemical complexes induce inflammation. They originate from: Plasma, (plasma derived mediaters). Cells, (cells derived mediaters).

Chemical mediators Plasma-derived: Complement, kinins, proteins & coagulation factors present in plasma. Many in “pro-form” requiring activation (enzymatic cleavage like proteolytic enzymes)

Chemical mediators Cell-derived: Preformed, sequestered and released (mast cell histamine, in intercellular granules of mast cells). Synthesized as needed (prostaglandin & cytokines).

The cells which release mediators These are; Platelets. Neutrophils. Monocytes. Macrophages. Mast cells.

Activation of Mediators Mediators are triggered by; Microbial products. Damaged tissue. By host proteins from; -Complement system. -Kinin system. -Clotting system.

Types of Chemical Mediaters Vasoactive amines: -Histamine. -Serotonin. Plasma proeases: -Complement system. -Kinin system. -Clotting system.

Types of Chemical Mediaters Arachidonic acid metabolies: -Prostaglandis. -Leukotriens. -Lipoxins. Platelet activating factors (PAF). Cytokines & Chemokines: -Tumor necrosis factors. -Inteleukin-1

Types of Chemical Mediaters Lysosomal constituents of leukocytes. Oxygen derived free radicals. Neuropeptides. Other mediates: -Hypoxia induce factor-1. -Necrotic tissue.

Chemical mediators Vasoactive amines: Histamines & Serotonin-1st mediaters released in inflammation. Mast cells, Basophils, Platelets & connective tissue (around the blood vessels), released histamine. Pre-formed histamine is present in mast cells granules.

Chemical mediators Vasoactive amines: Histamine is mainly released by mast cells granules in response of different stimuli: Physical injury- trauma, cold or heat. Immune reaction- binding of antibodies to mast cells.

Chemical mediators Vasoactive amines, (histamin release): Anaphylotoxins- C3a & C5a. Histamine releasing proteins- from leukocytes. Neuropeptides- substance P. Cytokines- IL-1 & IL-2.

Chemical mediators Functions of Histamine: - Dilation of arterioles. - Increase permeability of venules. - Constriction of large arteries.

Chemical mediators Serotonin: Pre-formed vasoactive mediater. Functions are same as Histamine. Activated by platelets aggregates. Serotonin & platelet aggregates are stimulated by platelet activating factor (PAF). Serotonin cause increase permeability during immunologic reaction.

Chemical mediators Plasma proteins: -Complement system. -Kinin system. -Clotting system.

Chemical mediators -Complement system: Consists of 20 component proteins with cleavage products. The system is consist of; Innate immunity. Adaptive immunity. Both types immunity act against microbial agents.

Chemical mediators -Complement activation causes: - Increased vascular permeablity. - Chemtaxis. - Opsonization.

Chemical mediators -Kinin system: Kinin system form the vasoactive peptides- Kininogens from the plasma proteins. Kinin system also release nonpeptide bradykinin- produce histamin like effect. Hog man factor also release bradykinin.

Chemical mediators -Kinin system: Function nonpeptide bradykinin: Increase vascular permeability. Dilation of blood vessels. Contraction of smooth muscles. Pain when injected in the skin.

Chemical mediators -Clotting system: It is divided into two; Intrinsic pathway. Extrinsic pathway.

Chemical mediators -Clotting system: Intrinsic pathway- is a series of plasma proteins, activated by Hogman factor (factor xii). Hogman factor (inactive protein) synthesized in liver. Hogman factor with negatively charged surfaces (collagen, platelets, basement membrane & in endothelial injury) form, factor XIIa & activate a verity of mediaters.

Chemical mediators Arachidonic acid metabolites: - Prostaglandins. - Leukotriens. - Lipoxins.

Chemical mediators Arachidonic acid metabolites: Arachidonic acid is a 20-carbon polyunsaturated fatty acid (from diet or from essential fatty acids). Present in cell membrane, as phospholipids. It release from cell membrane by phospholipase (phospholipase A2).

Chemical mediators Arachidonic acid metabolites: It release from cell membrane by phospholipase (phospholipase A2). The cellular phospholipase is activated by; Mechanical stimuli. Chemical stimuli. Physical stimuli. Mediaters like C5a.

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